Lecture 68

Question 1

pharmacokinetics

Answer 1

• how does the body affect the drug?
• ADME
• drug-drug/drug-herb interaction: a drug/herb alters another drug’s pharmacokinetics (absorption, distribution, metabolism, excretion)

pg 1757-1758

Question 2

pharmacodynamics

Answer 2

• how does the drug affect the body?
• drug-drug/drug-herb interaction: a drug/herb alters another drug’s action (increase or decrease)

pg 1757-1758

Question 3

pharmacokinetic drug interactions: absorption

Answer 3

a drug can alter another drug’s absorption by:

• formation of unabsorbable complex
• delaying gastric emptying → slows down drug absorption from the intestine
• changing the pH of the GI → affects drug solubility and absorption

pg 1768

Question 4

pharmacokinetic drug interactions: distribution

Answer 4

a drug can alter another drug’s distribution by:

• displacement at plasma protein binding sites
• changing volume of distribution of a drug (e.g.: diuretic changes V_d of lithium)

pg 1768

Question 5

pharmacokinetic drug interactions: metabolism

Answer 5

a classic example of what can go wrong is CYP inducers and inhibitor

pg 1768

Question 6

pharmacokinetic drug interactions: excretion

Answer 6

a drug can alter another drug’s renal excretion by:

• changing urine pH (urine alkalinization → increases reabsorption of alkaline drugs/increases excretion of acidic drugs)
• interference with reabsorption and secretion carriers/transporters

pg 1768

Question 7

pharmacodynamic drug interactions: addition

Answer 7

1 + 1 = 2
drugs administered together have the same effect as if they were administered separately

pg 1769

Question 8

pharmacodynamic drug interactions: synergism

Answer 8

1 + 1 > 2
result of interaction is greater than the sum of the drugs used alone “supra-additive effect” (help each other work better)

pg 1769

Question 9

pharmacodynamic drug interactions: potentiation

Answer 9

1 + 0 > 1
a drug’s effect is increased by another agent that doesn’t really have an effect

pg 1769

Question 10

pharmacodynamic drug interactions: antagonism

Answer 10

the two drugs may or may not act on the same receptors

pg 1769

Question 11

receptor occupancy theory

Answer 11

response is directly proportional to the number of occupied receptors

drug + receptor → drug-receptor complex → biologic effect

pg 1772

Question 12

affinity

Answer 12

• does the drug “like” the receptor?
• can it fit?
• how well does it bind?
• Key-lock model analogy: does the key fit the lock?

pg 1773

Question 13

affinity vs intrinsic activity

Answer 13

• binding is needed to elicit a response, but it doesn’t mean an action will definitely follow
• for an action to follow, it needs to create the structural/conformational changes in the receptor that will elicit a response
• key-lock model analogy: after the key fits, is it going to turn the lock?
• affinity determines if the drug and receptor will form the drug-receptor complex
• intrinsic activity determines if the drug-receptor complex will elicit a biologic effect

pg 1774

Question 14

agonist vs antagonist

Answer 14

• natural ligand: key fits in (has affinity) and turns (has intrinsic activity) the lock (receptor)
• agonist: mimicked key fits in (has affinity) and turns (has intrinsic activity) the lock (receptor)
• antagonist: has the ability to bind a receptor (has affinity), but doesn’t elicit a response (NO intrinsic activity)

pg 1775

Question 15

agonists

Answer 15

• an agonist can bind to the primary site (where the natural ligand binds) and mimic its action
• OR
• it can bind to a different site on the same receptor (allosteric/secondary site)
• binding the allosteric site results in: increased affinity of ligand to primary site OR increased effect that results from the binding
• an agonist that binds the allosteric site is called a PAM (positive allosteric modulator) or allosteric activator

pg 1776

Question 16

antagonists

Answer 16

• antagonists themselves produce NO response (NOT a negative response
• they ONLY prevent/block the natural ligand/agonist from binding
• antagonists can be: competitive, non-competitive (irreversible inhibitors, allosteric inhibitors), functional

pg 1781

Question 17

competitive antagonists

Answer 17

• a competitive antagonist binds to the same primary site as the natural ligand/agonist
• fair competition → if the competitive antagonist has higher conc and/or affinity, it can displace the natural ligand/agonist from the primary binding site (and vice versa)
• the “winner” is the molecule that has higher concentration at the binding site and/or higher affinity to bind the receptor

pg 1782

Question 18

non-competitive antagonists

Answer 18

• a non-competitive antagonist cannot be displaced by higher concentrations of the agonist
• irreversible antagonist: strong bond with the primary site → once bound, cannot be displaced
• allosteric inhibitor (NAM): higher concentration of the agonist at the primary binding site will not displace the negative modulator at the allosteric site

pg 1783

Question 19

functional antagonists

Answer 19

natural antagonists

• histamine binds histamine receptors leading to bronchoconstriction
• epinephrine binds beta-receptors leading to bronchodilation

pg 1784

Question 20

partial agonists

Answer 20

• partial agonists cannot produce maximal response even at maximal receptor occupancy
• partial agonists display a “mixed agonist-antagonist” effect
• in the presence of a full agonist, a partial agonist precipitates withdrawal (forcing the molecules to release)
• in the absence of a full agonist, a partial agonist prevents/treats withdrawal (once molecules have released, they make the body happy by binding some)

pg 1787-1788

Question 21

partial agonists example

Answer 21

• buprenorphine used in treatment of opioid use disorder (OUD)
• due to its agonist action, it provides some pain relief and prevents opioid withdrawal symptoms
• but it does NOT produce the “high” that a full agonist, such as morphine, is capable of producing

pg 1791

Question 22

constitutive activity theory

Answer 22

• traditionally, unoccupied receptors were considered to be inactive
• we now know that some receptors can be active WITHOUT a ligand (have constitutive activity)
• that receptor has two forms that exist in equilibrium (R_a is active form and R_i is inactive form)

pg 1794

Question 23

inverse agonist - mechanism of action

Answer 23

• inverse agonist: stabilizes the inactive form of the receptor, shifting equilibirum towards formation of more R_i; response: negative (does opposite function)
• antagonist: equal affinity to both forms; NO response (just blocks agonist binding)
• agonist: stabilizes the active form of the receptor, shifting equilibrium towards formation of more R_a; response: positive

pg 1795